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Sustained High Cure Rate of Artemether-Lumefantrine against Uncomplicated Plasmodium falciparum Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania.

Abstract We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. Patients with acute uncomplicated P. falciparum malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007-2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012-2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2-100), 122/127 (96.1%) (95% CI, 92.6-99.5), and 206/207 (99.5%) (95% CI, 98.6-100) in 2007-2008, 2012-2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ(2)trend test = 0.06, P = 0.90). Pretreatment P. falciparum multidrug-resistant gene 1 (Pfmdr1) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (P < 0.001), and P. falciparum chloroquine resistance transporter gene (Pfcrt) K76 prevalence increased significantly from 24/47 (51.1%) in 2006 to 198/205 (96.6%) in 2014 (P < 0.001). The AL cure rate remained high after 8 years of its wide-scale use in Bagamoyo district for the treatment of uncomplicated P. falciparum malaria despite an increase in prevalence of pretreatment Pfmdr1 N86 and Pfcrt K76 between 2006 and 2014.
PMID
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Authors

Mayor MeshTerms

Drug Therapy, Combination

Keywords
Journal Title the american journal of tropical medicine and hygiene
Publication Year Start




PMID- 28829723
OWN - NLM
STAT- MEDLINE
DA  - 20170822
DCOM- 20170911
LR  - 20170911
IS  - 1476-1645 (Electronic)
IS  - 0002-9637 (Linking)
VI  - 97
IP  - 2
DP  - 2017 Aug
TI  - Sustained High Cure Rate of Artemether-Lumefantrine against Uncomplicated
      Plasmodium falciparum Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo
      District, Tanzania.
PG  - 526-532
LID - 10.4269/ajtmh.16-0780 [doi]
AB  - We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 
      years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum 
      malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was
      performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014.
      Patients with acute uncomplicated P. falciparum malaria were enrolled, treated
      with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013),
      or 56 (2007-2008) days for clinical and laboratory evaluation. Primary outcome
      was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from
      2007 to 2014. Parasite clearance was slower for the 2006 and 2007-2008 cohorts
      with less than 50% of patients cleared of parasitemia on day 1, but was rapid for
      the 2012-2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%)
      (95% confidence interval [CI], 97.2-100), 122/127 (96.1%) (95% CI, 92.6-99.5),
      and 206/207 (99.5%) (95% CI, 98.6-100) in 2007-2008, 2012-2013, and 2014,
      respectively. There was no significant change in the trend of cure rate between
      2007 and 2014 (chi2trend test = 0.06, P = 0.90). Pretreatment P. falciparum
      multidrug-resistant gene 1 (Pfmdr1) N86 prevalence increased significantly across
      years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (P &lt; 0.001), and P.
      falciparum chloroquine resistance transporter gene (Pfcrt) K76 prevalence
      increased significantly from 24/47 (51.1%) in 2006 to 198/205 (96.6%) in 2014 (P 
      &lt; 0.001). The AL cure rate remained high after 8 years of its wide-scale use in
      Bagamoyo district for the treatment of uncomplicated P. falciparum malaria
      despite an increase in prevalence of pretreatment Pfmdr1 N86 and Pfcrt K76
      between 2006 and 2014.
FAU - Mwaiswelo, Richard
AU  - Mwaiswelo R
AD  - Department of Parasitology and Medical Entomology, Muhimbili University of Health
      and Allied Sciences, Dar es Salaam, Tanzania.
FAU - Ngasala, Billy
AU  - Ngasala B
AD  - Department of Parasitology and Medical Entomology, Muhimbili University of Health
      and Allied Sciences, Dar es Salaam, Tanzania.
FAU - Gil, J Pedro
AU  - Gil JP
AD  - Drug Resistance Unit, Division of Pharmacogenetics, Department of Physiology and 
      Pharmacology, Karolinska Institutet, Stockholm, Sweden.
FAU - Malmberg, Maja
AU  - Malmberg M
AD  - Section of Virology, Department of Biomedical Sciences and Veterinary Public
      Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
FAU - Jovel, Irina
AU  - Jovel I
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet,
      Stockholm, Sweden.
FAU - Xu, Weiping
AU  - Xu W
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet,
      Stockholm, Sweden.
FAU - Premji, Zul
AU  - Premji Z
AD  - Department of Parasitology and Medical Entomology, Muhimbili University of Health
      and Allied Sciences, Dar es Salaam, Tanzania.
FAU - Mmbando, Bruno P
AU  - Mmbando BP
AD  - National Institute for Medical Research, Tanga Centre, Tanga, Tanzania.
FAU - Bjorkman, Anders
AU  - Bjorkman A
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet,
      Stockholm, Sweden.
FAU - Martensson, Andreas
AU  - Martensson A
AD  - Department of Women's and Children's Health, International Maternal and Child
      Health (IMCH), Uppsala University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Trop Med Hyg
JT  - The American journal of tropical medicine and hygiene
JID - 0370507
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Ethanolamines)
RN  - 0 (Fluorenes)
RN  - C7D6T3H22J (artemether)
RN  - F38R0JR742 (lumefantrine)
SB  - AIM
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antimalarials/*therapeutic use
MH  - Artemisinins/*therapeutic use
MH  - *Drug Therapy, Combination
MH  - Ethanolamines/*therapeutic use
MH  - Female
MH  - Fluorenes/*therapeutic use
MH  - Humans
MH  - Malaria, Falciparum/*drug therapy/*epidemiology
MH  - Male
MH  - Middle Aged
MH  - Prevalence
MH  - Tanzania/epidemiology
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 2017/08/23 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/08/23 06:00
AID - 10.4269/ajtmh.16-0780 [doi]
PST - ppublish
SO  - Am J Trop Med Hyg. 2017 Aug;97(2):526-532. doi: 10.4269/ajtmh.16-0780.